Phosphoinositides and Cell Growth

Abstract

Phosphoinositides are a class of membrane phospholipids that serve as precursors to the important second messengers inositol(1,4,5)P3 and diacylglycerol, which mediate the release of intracellular calcium and the activation of protein kinase C, respectively.1,2 The key event in the production of these signals is the hydrolysis of phoshatidylinositol(4,5)P2 by phospholipase C. This traditional pathway of signal transduction is utilized by activated receptors for a variety of diverse stimuli, including hormones, growth factors, neurotransmitters and chemotactic factors. Recently, several new pathways of phosphoinositide (PI) metabolism have been discovered in cells stimulated by growth factors or transformed by certain oncogene products.1,3 These new pathways branch off the classical routes of PI hydrolysis and appear to be linked to poorly understood events in cellular regulation that are distinct from calcium release and C-kinase activation. In this discussion, several of these new aspects of PI metabolism relating to cell transformation will be illustrated, and a model for neoplastic transformation by the src tyrosine kinase oncogene, will be presented.